CCR5 regulates various aspects of the adaptive immune response. A nonfunctional allele resulting from a 32-bp deletion (CCR5-Δ32) causes loss of expression of the functional CCR5 receptor. CCR5 is a co-receptor for HIV and the CCR5-Δ32 allele reduces susceptibility to HIV infection. But there’s a problem. Homozygosity for the CCR5-Δ32 allele is a strong risk factor for symptomatic West Nile virus infection and also correlates with disease severity after tick-borne encephalitis virus infection. And now we know that CCR5 deficiency predisposes to fatal outcomes in influenza virus infection:
CCR5 deficiency predisposes to fatal outcome in influenza virus infection. J Gen Virol. 27 April 2015 doi: 10.1099/vir.0.000165
Influenza epidemics affect all age groups, although children, the elderly, and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50% of fatal cases, 25-50% of deaths are of apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-Δ32 mutation, a 32-base pair deletion in CCR5) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-Δ32 and evaluated its correlation with patient mortality. CCR5-Δ32 patients (17.4%) showed a higher mortality rate than wild-type individuals (4.7%; p = 0.021), which indicates that CCR5-Δ32 patients are at higher risk than the normal population of fatal outcome in influenza infection.